scholarly journals Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018–2019 Season

2019 ◽  
Vol 221 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Brendan Flannery ◽  
Rebecca J Garten Kondor ◽  
Jessie R Chung ◽  
Manjusha Gaglani ◽  
Michael Reis ◽  
...  

Abstract Background Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade. Methods Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants. Results During the 2018–2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%–51%) against A(H1N1)pdm09 and 9% (−4% to 20%) against A(H3N2); VE was 5% (−10% to 19%) against A(H3N2) clade 3C.3a viruses. Conclusions The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018–2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019–2020 northern hemisphere influenza vaccines.

Author(s):  
Mark W Tenforde ◽  
H Keipp Talbot ◽  
Christopher H Trabue ◽  
Manjusha Gaglani ◽  
Tresa M McNeal ◽  
...  

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.


2020 ◽  
Vol 71 (8) ◽  
pp. e368-e376 ◽  
Author(s):  
Jessie R Chung ◽  
Melissa A Rolfes ◽  
Brendan Flannery ◽  
Pragati Prasad ◽  
Alissa O’Halloran ◽  
...  

Abstract Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S292-S292
Author(s):  
Brendan L Flannery ◽  
Jessie Chung ◽  
Michael L Jackson ◽  
Lisa A Jackson ◽  
Arnold S Monto ◽  
...  

Abstract Background Interim estimates of 2017–2018 influenza vaccine effectiveness (VE) against influenza A(H3N2)-related illness in the United States indicated better protection among young children than among older children and adolescents. We examined VE against influenza A(H3N2) illness during five A(H3N2)-predominant seasons from 2010–2011 through 2016–2017 to investigate differences between VE among younger vs. older children. Methods We analyzed data from 11,736 outpatients aged <18 years with medically attended acute respiratory illnesses enrolled at US Flu VE Network study sites during five influenza A(H3N2)-predominant seasons. Respiratory specimens from all enrollees were tested for influenza viruses using reverse transcription PCR. Children with documented receipt of the recommended number of doses of current season inactivated influenza vaccine at least 14 days before illness onset were considered fully vaccinated; partially vaccinated children and those who received live attenuated influenza vaccine were excluded. Vaccine effectiveness was estimated as 100 × (1 – adjusted odds ratio) from multivariable logistic regression adjusting for study site, age, sex, presence of high-risk medical conditions, and days from illness onset to enrollment comparing odds of vaccination among A(H3N2)-positive cases vs. influenza-negative controls. Results A total of 1,854 influenza A(H3N2) cases and 9,882 influenza-negative controls were included; 494 (28%) influenza A(H3N2) cases and 3,637 (41%) controls were fully vaccinated before illness onset. VE ranged from 26% (95% confidence interval [CI], −17% to 53%) to 60% (38%–75%) among children aged 6 months–4 years and from 9% (−16% to 29%) to 66% (37%–82%) among 5–17 year olds (figure). During 2012–2013 and 2014–2015, A(H3N2) VE estimates were significantly higher among younger compared with older children (P < 0.05); in other seasons before 2017–2018, A(H3N2) VE estimates were similar among younger and older children. Conclusion Higher VE against A(H3N2) viruses in younger vs. older children in some seasons suggests immunologic differences in response to vaccine components. Overall, inactivated influenza vaccine provided moderate protection against A(H3N2)-related illness among children. Disclosures M. L. Jackson, sanofi pasteur: Grant Investigator, Research support. L. A. Jackson, Novartis: Grant Investigator, Research support. R. K. Zimmerman, sanofi pasteur: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. Merck: Grant Investigator, Research support. M. P. Nowalk, Merck: Grant Investigator, Research support. Pfizer: Grant Investigator, Research support. M. R. Griffin, MedImmune: Grant Investigator, Research support. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. J. J. Treanor, Novartis: Board Member and Consultant, Consulting fee.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S60-S60
Author(s):  
Ashley Fowlkes ◽  
Hannah Friedlander ◽  
Andrea Steffens ◽  
Kathryn Como-Sabetti ◽  
Dave Boxrud ◽  
...  

Abstract Background Due to marked variability in circulating influenza viruses each year, annual evaluation of the vaccine’s effectiveness against severe outcomes is essential. We used the Minnesota Department of Health’s (MDH) Severe Acute Respiratory Illness (SARI) surveillance to evaluate vaccine effectiveness (VE) against influenza-associated hospitalization over three influenza seasons. Methods Residual respiratory specimens from patients admitted with SARI were sent to the MDH laboratory for influenza RT-PCR testing. Medical records were reviewed to collect patient data. Vaccination history was verified using the state immunization registry. We included patients aged ≥6 months to < 13 years, after which immunization reporting is not required, hospitalized from the earliest influenza detection after July through April each year. We defined vaccinated patients as those ≥1 dose of influenza vaccine in the current season. Children aged < 9 years with no history of vaccination were considered vaccinated if 2 were doses given a month apart. Partially vaccinated children were excluded. We estimated VE as 1 minus the adjusted odds ratio (x100%) of influenza vaccination among influenza cases vs. negative controls, controlling for age, race, days from onset to admission, comorbidities, and admission month. Results Among 2198 SARI patients, 763 (35%) were vaccinated for influenza, 180 (8.2%) were partially vaccinated, and 1255 (57%) were unvaccinated. Influenza was detected among 202 (9.2%) children, and significantly more frequently among children aged ≥5 years (17%) compared with younger children (7.4%). The adjusted VE in 2013–14 was 68% (95% Confidence Interval: 34, 85), but was non-significant during the 2014–15 and 2015–16 seasons (Figure). Estimates of VE by influenza A subtypes varied substantially by year; VE against influenza B viruses was significant, but could not be stratified by year. VE was impacted when live attenuated influenza vaccine recipients were excluded. Conclusion We report moderately high influenza VE in 2013–14 and a point estimate higher than other published estimates from outpatient data in 2014–15. These results, underscore the importance of influenza vaccination to prevent severe outcomes such as hospitalization. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S26-S27
Author(s):  
Angela P Campbell ◽  
Constance E Ogokeh ◽  
Craig McGowan ◽  
Brian Rha ◽  
Rangaraj Selvarangan ◽  
...  

Abstract Background Annual national estimates of influenza vaccine effectiveness (VE) typically measure protection against outpatient medically attended influenza illness. We assessed influenza VE in preventing laboratory-confirmed influenza hospitalization in children across two influenza A(H3N2)-predominant seasons. Methods Children < 18 years hospitalized with acute respiratory illness were enrolled at 7 pediatric hospitals in the New Vaccine Surveillance Network. We included subjects ≥6 months with ≤10 days of symptoms enrolled during the 2016–2017 and 2017–2018 seasons (date of first through last influenza-positive case for each site). Combined mid-turbinate and throat swabs were tested using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare the odds of vaccination among cases positive for influenza with controls testing negative, adjusting for age, enrollment month, site, underlying comorbidities, and race/ethnicity. Full/partial vaccination was defined using ACIP criteria. We verified vaccine receipt from state immunization registries and/or provider records. Results Among 3441 children with complete preliminary data, in 2016–2017, 156/1,710 (9%) tested positive for influenza: 91 (58%) with influenza A(H3N2), 5 (3%) with A(H1N1), and 60 (38%) with B viruses. In 2017–2018, 193/1,731 (11%) tested positive: 87 (45%) with influenza A(H3N2), 47 (24%) with A(H1N1), and 58 (30%) with B. VE for all vaccinated children (full and partial) against any influenza was 48% (95% confidence interval, 26%–63%) in 2016–2017 and 45% (24%–60%) in 2017–2018. Combining seasons, VE for fully and partially vaccinated children against any influenza type was 46% (32%–58%); by virus, VE was 30% (4%–49%) for influenza A(H3N2), 71% (46%–85%) for A(H1N1), and 57% (36%–70%) for B viruses. There was no statistically significant difference in VE by age or full/partial vaccination status for any virus (table). Conclusion Vaccination in the 2016–2017 and 2017–2018 seasons nearly halved the risk of children being hospitalized with influenza. These findings support the use of vaccination to prevent severe illness in children. Our study highlights the need for a better understanding of the lower VE against influenza A(H3N2) viruses. Disclosures All Authors: No reported Disclosures.


Author(s):  
J M Ferdinands ◽  
M Gaglani ◽  
S Ghamande ◽  
E T Martin ◽  
D Middleton ◽  
...  

Abstract We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was −2% (95%CI −65, 37) and differed significantly by age, with VE of −130% (95% CI −374, −27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.


2021 ◽  
Author(s):  
Jin Gao ◽  
Xing Li ◽  
Hongquan Wan ◽  
Zhiping Ye ◽  
Robert Daniels

Neuraminidase (NA or N) antigens in circulating influenza viruses are not extensively evaluated for vaccine strain selection like hemagglutinin (HA or H) even though viral-based influenza vaccines include the recommended strain NA in varying amounts. As NA can also elicit a protective response, we assessed the antigenic similarity of the NAs from human H1N1 and H3N2 viruses that were prevalent between September 2019 to December 2020 to NAs from several recently recommended vaccine strains. To eliminate the dependence on isolates, the enzyme-linked lectin assay for analyzing NA antigenicity was performed with reverse genetic viruses carrying the same HA. Our results show that ferret antisera against NAs from the recommended H1N1 and H3N2 vaccine strains for the 2020-21 northern hemisphere influenza season recognize and inhibit the most prevalent circulating N1s and N2s, suggesting the NAs from the influenza A vaccine and circulating strains are antigenically similar. Comparisons of the recent N2s also revealed a bias in the reactivity of NA antisera from the egg and cell-based H3N2 vaccine strains due to a C-terminal substitution, indicating the C-terminus can influence N2 antigenicity and should receive consideration during the H3N2 strain selection.


2017 ◽  
Vol 22 (41) ◽  
Author(s):  
Marc Rondy ◽  
Alin Gherasim ◽  
Itziar Casado ◽  
Odile Launay ◽  
Caterina Rizzo ◽  
...  

In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65–79-year-olds and 13% (95% CI: −15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S962-S962
Author(s):  
Chandresh N Ladva ◽  
Edward Belongia ◽  
Arnold Monto ◽  
Emily T Martin ◽  
Manjusha Gaglani ◽  
...  

Abstract Background During 2017–2018, influenza vaccine effectiveness (VE) against A(H3N2) illness was highest among children <5 years compared with all other ages. A child’s first influenza infection can shape later immune responses. The emergence of antigenically distinct influenza A(H3N2) viruses in 2014–2015 provided an opportunity to explore potential effects of first virus infection on vaccine effects. We compared VE against influenza A(H3N2) during 2016–2017 and 2017–2018 among children born after and before 2014. Methods Outpatient children aged 6 months–17 years with acute respiratory illness with cough were enrolled in the United States Influenza VE Network and tested for influenza infection by RT–PCR. Vaccination status was derived through medical records and immunization registries. Children with partial or unknown vaccination status were excluded. We used a test-negative design to estimate VE and 95% confidence intervals (CI) from logistic regression, adjusting for potential confounders. Cohorts were defined by birth after or before June 2014; we assumed exposure to the new A(H3N2) virus among children born after June 2014. Results During 2016–2017, among 2,545 children, 445 (18%) tested positive for A(H3N2) and 1,809 (71%) tested negative. VE against A(H3N2) did not differ among children born after June 2014 and among those born before June 2014 [49% (95% CI: −12%, 77%) vs. 43% (27%, 55%); interaction P < 0.75]. During 2017–2018, among 2,936 patients, 631 (22%) tested positive for A(H3N2), and 1,852 (63%) tested negative. VE against A(H3N2) was 59% (36%, 74%) among children born after June 2014 vs. 20% (−1%, 37%) among those born before June 2014 (interaction P < 0.01). Conclusion We did not consistently see differences in VE against A(H3N2) between children potentially exposed to different A(H3N2) viruses. However, error in exposure assignment to A(H3N2) viruses and few seasons since the emergence of the new A(H3N2) viruses limit our interpretation. Future study will include additional A(H3N2) seasons as initial exposures to current circulating viruses increase among young children. Alternative explanations for age-related differences will also be explored, such as prior seasonal vaccination. Disclosures All authors: No reported disclosures.


Author(s):  
Constantina Boikos ◽  
Lauren Fischer ◽  
Dan O’Brien ◽  
Joe Vasey ◽  
Gregg C Sylvester ◽  
...  

Abstract Background The cell-propagated inactivated quadrivalent influenza vaccine (ccIIV4) may offer improved protection in seasons where egg-derived influenza viruses undergo mutations that affect antigenicity. This study estimated the relative vaccine effectiveness (rVE) of ccIIV4 versus egg-derived inactivated quadrivalent influenza vaccine (eIIV4) in preventing influenza-related medical encounters in the 2018-2019 U.S. season. Methods A dataset linking primary care electronic medical records with medical claims data was used to conduct a retrospective cohort study among individuals ≥4 years vaccinated with ccIIV4 or eIIV4 during the 2018-2019 season. Adjusted odds ratios (ORs) were derived from a doubly robust inverse probability of treatment-weighted approach adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness (rVE) was estimated by (1-OR)*100 and presented with 95% confidence intervals (CI). Results Following the application of inclusion/exclusion criteria, the study cohort included 2,125,430 ccIIV4 and 8,000,903 eIIV4 recipients. Adjusted analyses demonstrated a greater reduction in influenza-related medical encounters with ccIIV4 versus eIIV4, with the following rVE: overall, 7.6% (95% CI 6.5-8.6); age 4-17 years, 3.9% (0.9-7.0); 18-64 years, 6.5% (5.2-7.9); 18-49 years, 7.5% (5.7-9.3); 50-64 years, 5.6% (3.6-7.6); and ≥65 years, -2.2% (-5.4 to 0.9). Conclusions Adjusted analyses demonstrated statistically significantly greater reduction in influenza-related medical encounters in individuals vaccinated with ccIIV4 vs eIIV4 in the 2018-2019 U.S. influenza season. These results support ccIIV4 as a potentially more effective public health measure against influenza than an egg-based equivalent.


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